Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Human scavenger protein AIM increases foam cell formation and CD36‐mediated oxLDL uptake | |
关键词: CD5L; Spα; macrophage; atherosclerosis; apoptosis; | |
DOI : 10.1189/jlb.1212660 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
AIMisexpressedbymacrophagesinresponsetoagonistsofthenuclearreceptorsLXR/RXR.Inmice,itactsasanatherogenicfactorbyprotectingmacrophagesfromtheapoptoticeffectsofoxidizedlipids.Inhumans,itisdetectedinatheroscleroticlesions,butnorolerelatedtoatherosclerosishasbeenreported.ThisstudyaimedtoinvestigatewhethertheroleofhAIMextendsbeyondinhibitingoxidizedlipid‐inducedapoptosis.Toaccomplishthisgoal,functionalanalysiswithhumanmonocyticTHP1cellsandmacrophagesdifferentiatedfromperipheralbloodmonocyteswereperformed.ItwasfoundthathAIMreducedoxLDL‐inducedmacrophageapoptosisandincreasedmacrophageadhesiontoendothelialICAM‐1byenhancingLFA‐1expression.Furthermore,hAIMincreasedfoamcellformation,asshownbyOilRedOandNileRedstaining,aswellasquantificationofcholesterolcontent.Thiswasnotaresultofdecreasedreversecholesteroltransport,ashAIMdidnotaffecttheeffluxsignificantlyfrom[3H]Cholesterol‐ladenmacrophagesdrivenbyplasma,apoA‐I,orHDL2acceptors.Rather,flowcytometrystudiesindicatedthathAIMincreasedmacrophageendocytosisoffluorescentoxLDL,whichcorrelatedwithanincreaseintheexpressionoftheoxLDLRCD36.Moreover,hAIMboundtooxLDLinELISAandenhancedthecapacityofHEK‐293cellsexpressingCD36toendocytoseoxLDL,asstudiedusingimmunofluorescencemicroscopy,suggestingthathAIMservestofacilitateCD36‐mediateduptakeofoxLDL.OurdatarepresentthefirstevidencethathAIMisinvolvedinmacrophagesurvival,adhesion,andfoamcellformationandsuggestasignificantcontributiontoatherosclerosis‐relatedmechanismsinthemacrophage...
【 授权许可】
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